Pokemon is an oncogenic transcription factor involved in cell growth, differentiation, and oncogenesis, but little is known about its role in human breast cancer. This study aimed to reveal the role of pokemon in breast cancer progression and patient survival and to understand the underlying mechanisms.
Tissue microarray analysis of breast cancer tissues from patients with complete clinicopathological data and more than 20 years' follow-ups was used to evaluate pokemon expression and its correlation with the progression and prognosis of the disease. DNA microarray analysis of MCF-7 cells that overexpress pokemon was used to identify pokemon target genes. Chromatin immunoprecipitation and site-directed mutagenesis were utilized to determine how pokemon regulates survivin expression, a target gene.
Pokemon was found to be overexpressed in 158 of 182 (86.8%) breast cancer tissues and its expression was correlated with tumor size (P = 0.0148) and lymph node metastasis (P = 0.0014). Pokemon expression led to worse overall (n = 175, P = 0.01) and disease-related (n = 79, P = 0.0134) patient survival. DNA microarray analyses revealed that in breast cancer cells MCF-7, Pokemon regulates the expression of at least 121 genes involved in several signaling and metabolic pathways, including antiapoptotic survivin. In clinical specimens, pokemon and survivin expression was highly correlated (n = 49, r = 0.6799, P <0.0001). Chromatin immunoprecipitation and site-directed mutagenesis indicated that pokemon induces survivin expression by binding to the GT-boxes in its promoter.
Pokemon promotes breast cancer progression through upregulating survivin expression and thus may be a potential target for the treatment of this malignancy.
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